위조 의약품 근절을 위한 신기술

위조 의약품의 불법 거래는 수익성이 높고 광범위하게 퍼져 있는 사업이며, 개발도상국에 심각한 영향을 미치고 있습니다. 미국 식품의약국(FDA)에 따르면, 아시아, 라틴 아메리카, 사하라 이남 아프리카 지역 의약품의 최대 30%가 위조품이거나 품질 미달입니다.

그러나 이 문제는 저소득 및 중소득 국가에만 국한되지 않습니다. 온라인 약국이 약 4만 개로 추산될 정도로 급증함에 따라, 선진국에서도 위조 의약품이 더욱 흔해지고 있습니다.

위조 의약품으로 인한 위험은 매우 다양합니다. 질병 치료 실패라는 명백한 위험 외에도 위험한 성분, 부적절한 용량, 약물 상호작용으로 인한 심각한 부작용이나 사망에 이를 수 있습니다. 또한 위조 의약품은 의료 시스템에 대한 대중의 신뢰를 떨어뜨려 주요 보건 문제를 야기합니다(그림 1 참조). 잘못된 정보가 만연한 시대에 환자에게 안전하고 효과적인 치료제를 제공하는 것은 매우 중요하며, 여기에는 위조 의약품 및 유해 의료 제품을 근절하는 노력이 포함됩니다.

다행히 연구자들은 위조를 방지하기 위한 기술 개발에 진전을 보이고 있습니다. 의약품을 보호하는 포장재부터 알약 자체의 표면과 구조에 이르기까지, 의약품의 진위 여부를 확인하기 위한 다양한 전략이 탐구되고 있습니다. 육안으로 확인할 수 있는 방법도 있고, 첨단 기술을 사용하여 의약품이나 포장을 스캔하고 검증하는 방법도 있습니다. 이러한 모든 기술은 위조 의약품 퇴치에 중요한 돌파구가 될 수 있습니다.

가장 흔하게 위조되는 의약품은 무엇인가?

전 세계적으로 다양한 치료 영역의 의약품이 위조되고 있지만, 최근 연구에 따르면 위조범들은 탈모나 발기부전과 같은 비치명적 질환 치료제에서 생명을 위협하는 질환 치료제로 범위를 넓히고 있습니다. 예를 들어, 비아그라나 시알리스와 같은 약물은 흔히 위조되지만, 이제는 항우울제나 중추신경계 치료제에 대한 위조도 증가하고 있습니다. 2023년 제약보안연구소(Pharmaceutical Security Institute)는 위조의 주요 표적이 되는 5대 치료 영역을 다음과 같이 보고했습니다(그림 2).

항감염제 카테고리에는 항균제, 항바이러스제, 항진균제, 항말라리아제가 포함됩니다. 이 범주의 위조 의약품은 HIV나 말라리아 환자에게 해를 끼칠 수 있으며, 부적절한 용량 투여로 인한 항생제 내성 등 여러 위험을 초래할 수 있습니다.

위조 의약품 근절을 위한 기술적 진보

To combat this growing threat, pharmaceutical companies and regulatory authorities are turning to advanced technologies to authenticate medications and deter counterfeiters. One approach is advanced package labeling technologies, such as blockchain, radio frequency identification (RFID), holograms, QR codes, and 2D barcodes.

Several patents have been filed for advanced labeling, such as a process for adding hidden security features to packaging that can be revealed with a laser pointer (US20150183257A1 ), and Nuceria Adesivi S.r.l. patenting the indelible printing of the traceability code for pharmaceutical stickers (EP3130474 A2 [2017]). Companies like Authentix, Inc. and Alp Vision are also working on numerous forms of encrypted printing, holograms, and packaging identifiers.

However, package labeling can be ineffective if drugs are repackaged at any point along the supply chain. As a result, “on-drug labeling” is also being explored to prevent counterfeits from reaching patients. Here are five emerging technologies to stop counterfeits:

• DNA tagging incorporates unique DNA markers into drug formulations. This method is difficult to replicate and easy to verify, making it effective against counterfeiting. However, this technology has drawbacks like requiring costly, specialized equipment. An example of this technology was patented by the University of Southern California, using RFID and DNA taggant authentication systems and methods to prevent counterfeit, gray, and black-market pharmaceutical, medical, and other products (US7710269 B2 [2010]). The company Applied DNA Sciences, Inc., provides molecular tagging and DNA markers for similar operations.‍
• Blind watermarking embeds binary digits (bits) onto the surface of Fused Deposition Modeling (FDM) 3D-printed tablets. The benefit of this process is that it doesn’t impact the appearance, weight, or API content of medications, nor the printing time needed to make the tablets. Further, a computer, FDM 3D printer, and a paper scanner are all that are needed for detection. However, this process only works on straight, flat tablets, and only certain polymers can be used.
• ‍CandyCodes are edible identifiers unique to each pill, tablet, or capsule to which they’re applied. These identifiers are just what their name suggests — they’re nonpareils, the same tiny candy spheres used as decorations on desserts. When applied at random to legitimate drugs during manufacturing, the patterns can then be photographed and stored in a database. A patient would only have to upload a picture from their phone’s camera to the manufacturer’s database to verify that their medications are real.
  
  Since the chances of a random pattern of candy sprinkles being reproduced at random again by a counterfeiter are miniscule, this is a simple, scalable, and relatively inexpensive method to protect drug supplies. The main roadblock to implementing this technology is creating and maintaining a global database of these identifiers and keeping it secure from hacks and data breaches. The firm McNeill-PPC, Inc., explored a similar approach in an earlier patent filing (US20060088585 A1 [2006]) using a microrelief surface, which demonstrates that physical surface modification of individual doses may be a viable technique if data management issues can be addressed.

• Edible Physical Unclonable Functions (ePUFs) also use surface modifications on drugs. In this method, electrospray deposition uses strong electric fields to atomize a liquid suspension onto the surface of drug tablets. For ePUF authentication, researchers used a machine vision approach with the open-source SIFT pattern matching algorithm. The Purdue Research Foundation has also explored this process in a recent patent (WO2021076217 A1 [2021]).
  
  These surface depositions have the benefit of being extremely secure because they can’t be altered or removed. Patients can see them with the naked eye, and a simple phone camera picture can be used to verify that they’re not counterfeit. The main drawback is that automated manufacturing processes are required to achieve higher throughputs, and like CandyCodes, any manufacturer’s database would require management and security.‍
• Hidden imaging with peptide nanodots embeds these nanoparticles in polymer films. By selectively photo-bleaching the nanodots with a focused light source, hidden images or patterns can be created within the films. This approach has several benefits. First, the patterns remain stable, making his technique suitable for long-term storage of information. Peptide nanodots are also biocompatible. However, this method has some limitations in that the polymer films can eventually degrade over time. The limited color palette for nanodots could restrict the complexity of images that can be created, thereby limiting this method’s efficacy. Reading the hidden images also requires specialized equipment that would need to be scaled up and easier to obtain.

What’s at stake

Implementing these and other emerging technologies is more important as the threat from counterfeit pharmaceuticals increases. With the growth in online and mail-order pharmacies, more fake drugs are being sold, sometimes up to 50% of the medicines purchased from these pharmacies. Often operated in regions with lax oversight or regulation, these pill mills are mostly illegal.

Yet, the value of the global counterfeit drug trade is estimated at over $4 billion a year. According to the not-for-profit Pharmaceutical Security Institute, in 2023, there were 6,987 reported counterfeit drug incidents in 142 countries, an increase of 4% from 2022 (see Figure 3). These threats to public health will continue as long as financial incentives exist to sell counterfeit drugs and the internet provides the means to do so, which makes it vital for researchers and pharmaceutical companies to implement innovative ways to thwart counterfeiters.

‍ A multi-faceted approach to prevent counterfeiting

The problem of counterfeit drugs is complex, geographically dispersed, and constantly changing. To meet this threat, the global community needs multiple technologies as well as robust regulatory measures and partnerships. The World Health Organization (WHO) first published guidelines on combatting counterfeit drugs over 25 years ago, and efforts between the WHO, the United States, and other countries are continuing to refine new regulations.

Technologies from advanced package labeling to 3D printing to nanoparticles can make a difference in the fight against counterfeit drugs. With researchers leveraging AI, machine learning, and nanotechnologies, to name only a few, it’s possible that significant progress against the growing counterfeit drug trade is near.